ArticleNature chemical biology2023
Depletion of creatine phosphagen energetics with a covalent creatine kinase inhibitor.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.Nature chemical biology · 2026Article
- Mitochondrial ATP production promotes T cell differentiation and function by regulating chromatin accessibility.bioRxiv : the preprint server for biology · 2026Article
- Biocompatible ligand balancing in transition metal coordination enables benign in-cell protein arylation.Nature chemistry · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.bioRxiv : the preprint server for biology · 2026Article
- Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells.ACS chemical biology · 2025Article
- Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin.Cancer cell international · 2025Article
- Creatine Kinase Blockade Disrupts Energy Metabolism and Redox Homeostasis to Suppress Osteosarcoma Progression.International journal of molecular sciences · 2025Article
- Creatine kinase imaging (CKI) for in vivo whole-brain mapping of creatine kinase reaction kinetics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrative multi-omics analysisiScience · 2025Article
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- Gas Phase Separation of Modified Peptides for Activity-Based Protein Profiling.Analytical chemistry · 2025Article
- Structural basis for substrate binding, catalysis, and inhibition of cancer target mitochondrial creatine kinase by a covalent inhibitor.Structure (London, England : 1993) · 2025Article
- The human zinc-binding cysteine proteome.Cell · 2025Article
- Targeting Creatine and Creatine Kinase in Cancer: Exploring Potential Therapeutic Strategies.Current drug targets · 2025Review
- It Is Not Just About Storing Energy: The Multifaceted Role of Creatine Metabolism on Cancer Biology and Immunology.International journal of molecular sciences · 2024Review
- Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
- Multi-tiered chemical proteomic maps of tryptoline acrylamide-protein interactions in cancer cells.Nature chemistry · 2024Article
- Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway.Acta pharmaceutica Sinica. B · 2024Article
- A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.Scientific reports · 2024Article
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Creatine kinases (CKs) provide local ATP production in periods of elevated energetic demand, such as during rapid anabolism and growth. Thus, creatine energetics has emerged as a major metabolic liability in many rapidly proliferating cancers. Whether CKs can be targeted therapeutically is unknown because no potent or selective CK inhibitors have been developed. Here we leverage an active site cysteine present in all CK isoforms to develop a selective covalent inhibitor of creatine phosphagen energetics, CKi. Using deep chemoproteomics, we discover that CKi selectively engages the active site cysteine of CKs in cells. A co-crystal structure of CKi with creatine kinase B indicates active site inhibition that prevents bidirectional phosphotransfer. In cells, CKi and its analogs rapidly and selectively deplete creatine phosphate, and drive toxicity selectively in CK-dependent acute myeloid leukemia. Finally, we use CKi to uncover an essential role for CKs in the regulation of proinflammatory cytokine production in macrophages.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.